Immunodeficiency Virus Type 1, Human
Conditions
Keywords
Immunodeficiency Virus Type 1, Human, Darunavir, Cobicistat, Tenofovir Alafenamide, Emtricitabine, Tenofovir Disoproxil Fumarate
Brief summary
The purpose of this study is to demonstrate non-inferiority in efficacy of a darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed dose combination (FDC) tablet versus Darunavir/Cobicistat (DRV/COBI) FDC coadministered with Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) FDC in human immunodeficiency virus-1 (HIV-1) infected, antiretroviral (ARV) treatment naive adult participants.
Detailed description
This is a Phase 3, multicenter (when more than one hospital or medical school team work on a medical research study), randomized (study drug assigned by chance), double-blind (a medical research study in which neither the researchers nor the participant know what treatment the participant is receiving), active-controlled (study in which the experimental treatment or procedure is compared to a standard \[control\] treatment or procedure) study. The study consists of 5 periods: a Screening period, Double-blind treatment period, Single-arm treatment period, Extension period and a Follow-up period. Participants will receive either darunavir (DRV)/ cobicistat (COBI)/emtricitabine (FTC) /tenofovir alafenamide (TAF) fixed dose combination (D/C/F/TAF FDC) or DRV/COBI FDC along with FTC/TDF FDC. Primarily percentage of participants with human immunodeficiency virus (HIV) -1 Ribonucleic acid (RNA) less than (\<) 50 copies per milliliter (copies/ml) defined by snapshot analysis will be evaluated. Participants' safety will be monitored throughout the study.
Interventions
A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF) 10 mg will be administered once daily.
DRUGDRV/COBI FDC
A tablet containing DRV 800 mg and COBI 150 mg will be administered once daily.
DRUGFTC/TDF FDC
A tablet containing FTC 200 mg and TDF 300 mg will be administered once daily.
DRUGD/C/F/TAF FDC - Matching Placebo
Matching placebo of D/C/F/TAF FDC will be administered once daily.
DRUGFTC/TDF FDC Matching Placebo
Matching placebo of FTC/TDF FDC will be administered once daily.
DRUGDRV/COBI FDC Matching Placebo
Matching placebo of DRV/COBI FDC will be administered once daily.
Sponsors
Janssen Sciences Ireland UC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject must be antiretroviral (ARV) treatment-naive (never treated with an ARV including post-exposure prophylaxis and pre-exposure prophylaxis); no prior use of any approved or experimental anti- human immunodeficiency virus (anti-HIV) drug for any length of time * Screening plasma HIV-1 ribonucleic acid (RNA) level greater than or equal to \>=1,000 copies per milliliter (copies/mL) * Cluster of Differentiation 4+ (CD4+) cell count \>50 cells/microliter (cells/mcL) * Screening HIV-1 genotype report must show full sensitivity to DRV, TDF and FTC * Screening eGFRcreatinine \>=70 mL/min according to the Cockcroft-Gault formula for creatinine clearance
Exclusion criteria
* Subject has been diagnosed with a new acquired immunodeficiency syndrome (AIDS)-defining condition within the 30 days prior to screening * Subject has proven or suspected acute hepatitis within 30 days prior to screening * Subject is hepatitis C or hepatitis B positive * Subject has a history of cirrhosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies Per Milliliter (Copies Per mL) (Virologic Response) at Week 48 Defined by Food and Drug Administration (FDA) Snapshot Approach | At Week 48 | Percentage of participants with a HIV-1 RNA \< 50 copies per mL were assessed using FDA snapshot approach which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. The snapshot approach classified participants into 3 outcome categories: 1) virologic success (HIV RNA \< 20/50/200 copies per mL at Week 48), 2) virologic failure (HIV RNA greater than or equal to \[\>=\] 20/50/200 copies per mL at Week 48), 3) no viral load data in the Week 48 visit window (discontinued due to adverse event/death/other reason). The missing HIV-1 RNA is considered as non-response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | At Week 48 and 96 | Percentage of participants with HIV-1 RNA less than (\<) 20, 50, and 200 copies per mL at Weeks 48 and 96 based on TLOVR algorithm were assessed. TLOVR requires sustained HIV-1 RNA \< 50 copies per mL; confirmed HIV-1 RNA \>= 50 copies per mL is considered as non-response (rebound); participant is considered non-responder after permanent discontinuation. |
| Change From Baseline in log10 HIV-1 RNA Levels at Week 48 | Baseline and Week 48 | Change from baseline in log10 HIV-1 RNA levels were reported. |
| Change From Baseline in Cluster of Differentiation-4 (CD4+) Cell Count at Week 48 | Baseline and Week 48 | The immunologic change was determined by changes in Cluster of CD4+ cell count. Change from baseline in CD4+ cell count at Week 48 were assessed. |
| Change From Baseline in Serum Creatinine at Week 48 | Baseline and Week 48 | Change from baseline in serum creatinine at Week 48 was reported. |
| Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Formula at Week 48 | Baseline and Week 48 | Change from baseline in eGFRcr was calculated using the CKD-EPI equation as per which Stage 1 (normal or high GFR \[\>=90 mL/min\]); Stage 2 (Mild CKD \[60 to 90 mL/min\]); Stage 3 (Moderate CKD \[30 to 59mL/min\]); Stage 4 (Severe CKD \[15 to 29 mL/min\]); Stage 5 (End Stage CKD \[\<15 mL/min\]). The eGFRcr was assessed by calculating serum creatinine (Scr) using the equation: eGFRcr milliliter per minute per 1.72 meter square (mL/min/1.73m\^2) = 144\*(Scr/0.7)\^-0.329\*0.993\^age (Scr =\< 0.7 mg/dL) and eGFRcr mL/min/1.73m\^2 = 144\*(Scr/0.7)\^-1.209\*0.993\^age (Scr \>0.7 mg/dL) for female participants and eGFRcr mL/min/1.73m\^2 = 141\*(Scr/0.9)\^-0.411\*0.993\^age (Scr =\<0.9 mg/dL) and eGFRcr mL/min/1.73m\^2 = 141\*(Scr/0.9)\^-1.209\*0.993\^age (Scr \>0.9 mg/dL) for male participants. |
| Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine by (Cockcroft-Gault Formula) at Week 48 | Baseline and Week 48 | Change from baseline in eGFRcr by cockcroft-gault formula at Week 48. The eGFRcr was assessed by calculated creatinine clearance (CrCl) using the Cockcroft-Gault formula, and was assessed using CrCl \[mL/min\] = (140 - A) \* W / (72 \* C) \* R. Where A is age at sample date \[years\], W is body weight at specific visit (kilogram \[kg\]), C is the serum concentration of creatinine \[mg/dL\], R = 1 if the participant is male and = 0.85 if female. |
| Area Under the Plasma Concentration Time Curve Across the Dosing Interval (AUCtau) of Tenofovir Alafenamide | 30 minutes to 4 hours postdose at Weeks 2, 4, 12, 24 and 48 and at 2 timepoints with at least 2.5 hours in between sampling at Week 8 and 36 (first sample between 1 and 4 hours postdose) | The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption. |
| Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst) by CKD-EPI Formula at Week 48 | Baseline and Week 48 | Change from baseline in eGFRcyst was calculated using the CKD-EPI equation as per which Stage 1 (normal or high GFR) \>= 90 indicates normal kidney function; Stage 2 (Mild CKD): 60 to 89 mL/min indicates mildly reduced kidney function; Stage 3 (Moderate CKD): 30 to 59 mL/min indicates moderately reduced kidney function; Stage 4 (Severe CKD): 15 to 29 mL/min indicates severely reduced kidney function; Stage 5 (End Stage of CKD): \<15 mL/min indicate very severe or end stage kidney failure. The eGFRcyst was assessed by calculated serum cystatin C (Scyst) using the equation: eGFRcyst mL/min/1.73m\^2 = 133 \* (Scyst/0,8)\^-0.499 \* 0.996\^age \[\* 0.932 if female\] (Scyst =\<0.8 mg/L) and eGFRcr mL/min/1.73m\^2 = 133 \* (Scyst/0,8)\^-1.328 \* 0.996\^age \[\* 0.932 if male\] (Scyst \>0.8 mg/L). |
| Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 48 | Up to Weeks 48 | AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events. SAE is any adverse event (AE) that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. |
| Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Week 48 | Baseline and Week 48 | Change from baseline in UPCR at Week 48 was reported. |
| Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) at Week 48 | Baseline and Week 48 | Change from baseline in UACR at Week 48 was reported. |
| Change From Baseline in Urine Retinol Binding Protein To Creatinine Ratio (URBPCR) at Week 48 | Baseline and Week 48 | Change from baseline in URBPCR at Week 48 were reported. |
| Change From Baseline in Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Week 48 | Baseline and Week 48 | Change from baseline in UB2MGCR at Week 48 were reported. |
| Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Week 48 | Baseline and Week 48 | Percent change from baseline in FEPO4 at Week 48 was reported. |
| Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours Post-dose (AUC0-24h) of Darunavir | 0 to 24 hours post dose | AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours post-dose. |
| Predose (Trough) Plasma Concentration (C0h) of Darunavir | 30 minutes to 4 hours postdose at Weeks 2, 4, 12, 24 and 48 and at 2 timepoints with at least 2.5 hours in between sampling at Week 8 and 36 (first sample between 1 and 4 hours postdose) | C0h is defined as the predose (trough) plasma concentration or concentration just prior to study drug administration. |
| Plasma Concentrations 2 Hours After Dosing (C0-2h) of Tenofovir Alafenamide | 0 to 2 hours post dose | C0-2h is defined as the plasma concentrations 2 hours after dosing. |
| Percent Change From Baseline in Hip and Spine Bone Mineral Density (BMD) | Baseline, Weeks 24 and 48 | The BMD is the amount of mineral in gram per square centimeter of bone, which was assessed by dual energy x-ray absorptiometry (DEXA) scan. Positive values are best values and negative values are worst values of change. Percent change from baseline in hip and spine BMD was assessed. |
| Change From Baseline in BMD T-score of Hip and Spine | Baseline, Weeks 24 and 48 | BMD status was assessed using BMD T-scores; normal bone status was defined by a BMD T-score \>= -1, osteopenia by a T-score \>= -2.5 to \<-1.0, and osteoporosis by a T-score \<-2.5. |
| Change From Baseline in Alkaline Phosphatase (ALP) Levels at Weeks 24 and 48 | Baseline, Weeks 24 and 48 | Change from baseline in ALP at Weeks 24 and 48 was reported. |
| Change From Baseline in Levels of Serum Procollagen 1 N-Terminal Propeptide (P1NP) at Weeks 24 and 48 | Baseline, Weeks 24 and 48 | Change from baseline in serum P1NP at Weeks 24 and 48 were reported. |
| Change From Baseline in Levels of Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) at Weeks 24 and 48 | Baseline, Weeks 24 and 48 | Change from baseline in serum CTX at Weeks 24 and 48 were reported. |
| Change From Baseline in Levels of Parathyroid Hormone (PTH) at Weeks 24 and 48 | Baseline, Weeks 24 and 48 | Change from baseline in PTH at Weeks 24 and 48 were reported. |
| Change From Baseline in Levels of 25-Hydroxyvitamin D (25-OH Vitamin D), at Week 24 and 48 | Baseline, Weeks 24 and 48 | Change from baseline in 25-OH Vitamin D levels at Week 24 and 48 were reported. |
| Percentage of Participants With HIV-1 RNA <50 Copies Per mL at Week 96 Defined by FDA Snapshot Approach | At Week 96 | Percentage of participants with a HIV-1 RNA \< 50 copies per mL were assessed using FDA snapshot approach which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. The snapshot approach classified participants into 3 outcome categories: 1) virologic success (HIV RNA \< 20/50/200 copies per mL at Week 96), 2) virologic failure (HIV RNA greater than or equal to \[\>=\] 20/50/200 copies per mL at Week 96), 3) no viral load data in the Week 96 visit window (discontinued due to adverse event/death/other reason). The missing HIV-1 RNA is considered as non-response. |
| Change From Reference in log10 HIV-1 RNA Levels at Week 96 | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in log10 HIV-1 RNA levels were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for Test group and reference 2 is the last value prior to the switch for Control group. |
| Change From Reference in CD4+ Cell Count at Week 96 | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | The immunologic change was determined by changes in cluster of differentiation (CD4+) cell count. Change from reference in CD4+ cell count at Week 96 was assessed. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Percentage of Participants With >95% Treatment Adherence Assessed by Drug Accountability | Baseline to Switch and switch to EOE to Open-Label D/C/F/TAF (Up to 3 years) | Treatment adherence assessed by drug accountability (based on pill count) from start of treatment/switch to last study drug intake by determination of the cumulative treatment adherence in participants who returned all dispensed bottles prior to or at the last visit in the study. Adherent participants were defined as having an adherence \>95% as assessed by drug accountability. |
| Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 96 | Up to Week 96 | AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events. SAE is any adverse event (AE) that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. |
| Change From Reference in Serum Creatinine | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in serum creatinine was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Change From Reference in eGFRcr by CKD-EPI Formula | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in eGFRcr was calculated using the CKD-EPI equation as per Stage 1 (normal or high GFR) to Stage 5 (End Stage of CKD). The eGFRcr was assessed by calculating serum creatinine (Scr) using the CKD-EPI equation: eGFRcr milliliter per minute per 1.72 meter square (mL/min/1.73m\^2) = 144 \* (Scr/0.7)\^-0.329 \* 0.993\^age (Scr =\< 0.7 mg/dL) and eGFRcr mL/min/1.73m\^2 = 144 \* (Scr/0.7)\^-1.209 \* 0.993\^age (Scr \>0.7 mg/dL) for female participants and eGFRcr mL/min/1.73m\^2 = 141 x (Scr/0.9)\^-0.411 x 0.993\^age (Scr =\<0.9 mg/dL) and eGFRcr mL/min/1.73m\^2 = 141 \* (Scr/0.9)\^-1.209 x 0.993\^age (Scr \>0.9 mg/dL) for male participants. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine by Cockcroft-Gault Formula | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in eGFRcr by cockcroft-gault formula was reported. The eGFRcr was assessed by calculated creatinine clearance (CrCl) using the Cockcroft-Gault formula, and was assessed using CrCl \[mL/min\] = (140 - A) \* W / (72 \* C) \* R. Where A is age at sample date \[years\], W is body weight at specific visit (kilogram \[kg\]), C is the serum concentration of creatinine \[mg/dL\], R = 1 if the participant is male and = 0.85 if female. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst) by CKD-EPI Formula | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in eGFRcyst was calculated using the CKD-EPI equation as per Stage 1 (normal or high GFR) to Stage 5 (End Stage of CKD): \<15 mL/min indicate very severe or end stage kidney failure. The eGFRcyst was assessed by calculated serum cystatin C (Scyst) using the CKD-EPI equation: eGFRcyst mL/min/1.73m\^2 = 133 \* (Scyst/0,8)\^-0.499 \* 0.996\^age \[x 0.932 if female\] (Scyst =\<0.8 mg/L) and eGFRcr mL/min/1.73m\^2 = 133 \* (Scyst/0,8)\^-1.328 \* 0.996\^age \[\* 0.932 if male\] (Scyst \>0.8 mg/L). Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Change From Reference in UPCR | From Reference 1 to Week 96 for D/C/F/TAF+ FTC/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in UPCR was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Change From Reference in UACR | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in UACR at Week 96 was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Change From Reference in URBPCR | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in URBPCR at Week 96 were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Change From Reference in UB2MGCR | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in UB2MGCR was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Percent Change From Reference in Urine FEPO4 | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Percent change from reference in FEPO4 at Week 96 were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Percent Change From Reference in Hip and Spine BMD | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | The BMD is the amount of mineral in gram per square centimeter of bone, which was assessed by DEXA scan. Positive values are best values and negative values are worst values of change. Percent change from reference in hip and spine BMD was assessed. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Change From Reference in Levels of Serum CTX | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in serum CTX levels were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Change From Reference in BMD T-score of Hip and Spine at Week 96 | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | BMD status was assessed using BMD T-scores; normal bone status was defined by a BMD T-score \>= -1, osteopenia by a T-score \>= -2.5 to \<-1.0, and osteoporosis by a T-score \<-2.5. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Change From Reference in ALP Levels | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in ALP levels at Week 96 was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Change From Reference in Levels of Serum P1NP | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in serum P1NP levels were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Change From Reference in Levels of PTH | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in PTH levels were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Change From Reference in Levels of 25-OH Vitamin D | From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF | Change from reference in 25-OH Vitamin D were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group. |
| Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 to end of extension (up to 3 years) | Percentage of participants with HIV RNA \<50, \<20, and \<200 copies/mL post Week 96 to end of extension were reported. |
| Percentage of Participants With Protocol-defined Virologic Failure (PDVF) | From Baseline up to Week 96 | Percentage of participants with PDVF were reported. Protocol-defined virologic failure was defined as having virologic non-response (HIV-1 RNA \<1 log10 reduction from baseline and \>=50 copies/mL at the Week 8 visit, confirmed at the next visit), virologic rebound (confirmed HIV-1 RNA \>=50 copies/mL after confirmed consecutive HIV-1 RNA \<50 copies/mL or confirmed \>1 log10 increase in HIV-1 RNA from nadir), or viremic at final time point (final available on treatment HIV-1 RNA \>=400 copies/mL). |
| Percentage of Participants With HIV-1 RNA <20 and 200 Copies Per mL at Weeks 48 and 96 Defined by FDA Snapshot Approach | At Weeks 48 and 96 | Percentage of participants with HIV-1 RNA \< 20/200 copies per mL using FDA snapshot approach were reported. The snapshot approach classified participants into 3 outcome categories: 1) virologic success (HIV RNA \< 20/50/200 copies per mL at Week 48 and 96), 2) virologic failure (HIV RNA \>= 20/50/200 copies per mL at Week 48 and 96), 3) no viral load data in the Week 48 and 96 visit window (discontinued due to adverse event/death/other reason). The missing HIV-1 RNA is considered as non-response. |
| Percentage of Participants With PDVF Post-week 96 to End of Extension | Week 96 to end of extension (up to 3 years) | Percentage of participants with PDVF were reported. Protocol-defined virologic failure was defined as having virologic non-response (HIV-1 RNA \<1 log10 reduction from baseline and \>=50 copies/mL at the Week 8 visit, confirmed at the next visit), virologic rebound (confirmed HIV-1 RNA \>=50 copies/mL after confirmed consecutive HIV-1 RNA \<50 copies/mL or confirmed \>1 log10 increase in HIV-1 RNA from nadir), or viremic at final time point (final available on treatment HIV-1 RNA \>=400 copies/mL). |
| Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates | From Week 96 to end of extension (up to 2 years and 6 months) | Percentage of participants with non-PDVF by Kaplan-Meier Estimates were reported. PDVF was defined as having virologic non-response (HIV-1 RNA \<1 log10 reduction from baseline and \>=50 copies/mL at the Week 8 visit, confirmed at the next visit), virologic rebound (confirmed HIV-1 RNA \>=50 copies/mL after confirmed consecutive HIV-1 RNA \<50 copies/mL or confirmed \>1 log10 increase in HIV-1 RNA from nadir), or viremic at final time point (final available on treatment HIV-1 RNA \>=400 copies/mL). |
| Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates | From Week 96 to end of extension (up to 3 years) | Percentage of participants with time to treatment failure by Kaplan-Meier Estimates were reported. Treatment failure was defined as having either protocol-defined virologic failure or having discontinued for reasons other than alternate access to D/C/F/TAF (or other ARVs). |
| CD4+ Cell Count Post-Week From 96 to End of Extension | Week 96 to end of extension (up to 3 years) | The immunologic change was determined by Cluster of CD4+ cell count. CD4+ cell count post-Week 96 to end of extension were assessed. |
| Percentage of Participants With Grade 3 and 4 AEs, SAEs, and Premature Discontinuations Due to Adverse Events Post-Week 96 to End of Extension | From Week 96 to end of extension (up to 3 years) | AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events. SAE is any adverse event (AE) that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. |
| Number of Participants With ARV Resistance | Baseline to end of extension (up to 4 years) | Number of participants with DRV, FTC, TDF/TAF resistance were reported. |
Countries
Belgium, Canada, France, Germany, Poland, Puerto Rico, Russia, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) Participants received a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination \[FDC\]) once daily along with DRV/COBI FDC-matching placebo and FTC/tenofovir disoproxil fumarate (TDF) FDC-matching placebo tablets once daily up to Week 48 analysis unblinding visit (that is, after last participant has reached Week 48). After Week 48 analysis unblinding visit, all participants received D/C/F/TAF treatment up to Week 96 during the open-label, single-group treatment phase. After Week 96, participants were given the opportunity to continue D/C/F/TAF treatment during an extension phase until the D/C/F/TAF FDC tablet became commercially available. | 362 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) Participants received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily Subjects received DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48 analysis unblinding visit (that is, after last subject has reached Week 48). | 363 |
| Total | 725 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| BL to EOE-Test and BL to Switch- Control | Adverse Event | 12 | 16 | 0 |
| BL to EOE-Test and BL to Switch- Control | Death | 0 | 1 | 0 |
| BL to EOE-Test and BL to Switch- Control | Lost to Follow-up | 17 | 8 | 0 |
| BL to EOE-Test and BL to Switch- Control | Other | 11 | 2 | 0 |
| BL to EOE-Test and BL to Switch- Control | Physician Decision | 9 | 4 | 0 |
| BL to EOE-Test and BL to Switch- Control | Pregnancy | 1 | 1 | 0 |
| BL to EOE-Test and BL to Switch- Control | Subject non-compliant | 2 | 0 | 0 |
| BL to EOE-Test and BL to Switch- Control | Withdrawal by Subject | 14 | 9 | 0 |
| Switch to D/C/F/TAF (Until EOE) | Adverse Event | 0 | 0 | 5 |
| Switch to D/C/F/TAF (Until EOE) | Death | 0 | 0 | 1 |
| Switch to D/C/F/TAF (Until EOE) | Lost to Follow-up | 0 | 0 | 12 |
| Switch to D/C/F/TAF (Until EOE) | Other | 0 | 0 | 4 |
| Switch to D/C/F/TAF (Until EOE) | Physician Decision | 0 | 0 | 1 |
| Switch to D/C/F/TAF (Until EOE) | Withdrawal by Subject | 0 | 0 | 10 |
Baseline characteristics
| Characteristic | D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Total |
|---|---|---|---|
| Age, Continuous | 34 years | 34 years | 34.0 years |
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adults (18-64 years) | 362 Participants | 362 Participants | 724 Participants |
| Age, Customized Children (2-11 years) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized From 65 to 84 years | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 7 Participants | 11 Participants |
| Race/Ethnicity, Customized Black or African American | 40 Participants | 40 Participants | 80 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 41 Participants | 38 Participants | 79 Participants |
| Race/Ethnicity, Customized Other | 19 Participants | 18 Participants | 37 Participants |
| Race/Ethnicity, Customized White Non-Hispanic | 258 Participants | 260 Participants | 518 Participants |
| Sex: Female, Male Female | 44 Participants | 41 Participants | 85 Participants |
| Sex: Female, Male Male | 318 Participants | 322 Participants | 640 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 362 | 1 / 363 | 1 / 322 |
| other Total, other adverse events | 284 / 362 | 252 / 363 | 137 / 322 |
| serious Total, serious adverse events | 47 / 362 | 36 / 363 | 21 / 322 |
Outcome results
Primary
Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies Per Milliliter (Copies Per mL) (Virologic Response) at Week 48 Defined by Food and Drug Administration (FDA) Snapshot Approach
Percentage of participants with a HIV-1 RNA \< 50 copies per mL were assessed using FDA snapshot approach which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. The snapshot approach classified participants into 3 outcome categories: 1) virologic success (HIV RNA \< 20/50/200 copies per mL at Week 48), 2) virologic failure (HIV RNA greater than or equal to \[\>=\] 20/50/200 copies per mL at Week 48), 3) no viral load data in the Week 48 visit window (discontinued due to adverse event/death/other reason). The missing HIV-1 RNA is considered as non-response.
Time frame: At Week 48
Population: The intent-to-treat (ITT) analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here N (number of participants analyzed) refers to 362 for test group and 363 for control group.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies Per Milliliter (Copies Per mL) (Virologic Response) at Week 48 Defined by Food and Drug Administration (FDA) Snapshot Approach | 91.4 percentage of participants | 95% Confidence Interval 88.1 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies Per Milliliter (Copies Per mL) (Virologic Response) at Week 48 Defined by Food and Drug Administration (FDA) Snapshot Approach | 88.4 percentage of participants | 95% Confidence Interval 84.7 |
p-value: <0.00195% CI: [-1.6, 7.1]Mantel Haenszel
Secondary
Area Under the Plasma Concentration Time Curve Across the Dosing Interval (AUCtau) of Tenofovir Alafenamide
The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.
Time frame: 30 minutes to 4 hours postdose at Weeks 2, 4, 12, 24 and 48 and at 2 timepoints with at least 2.5 hours in between sampling at Week 8 and 36 (first sample between 1 and 4 hours postdose)
Population: PK analysis set included all participants who were randomized, received at least 1 dose of study drug and plasma concentration data for analytes of interest were available. PK data of TAF was analyzed only for test arm as per planned analyses. Here, 'N' (number of participants analyzed) number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Area Under the Plasma Concentration Time Curve Across the Dosing Interval (AUCtau) of Tenofovir Alafenamide | 132.3117 h*ng/mL | Standard Deviation 40.87742 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours Post-dose (AUC0-24h) of Darunavir
AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours post-dose.
Time frame: 0 to 24 hours post dose
Population: Pharmacokinetic (PK) analysis set included all participants who were randomized, received at least 1 dose of study drug and plasma concentration data for analytes of interest were available. PK data of DRV was analyzed only for test arm as per planned analyses. Here, 'N' (number of participants analyzed) number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours Post-dose (AUC0-24h) of Darunavir | 87909.3282 hours*nanogram per milliliter (h*ng/mL) | Standard Deviation 20232.09905 |
Secondary
CD4+ Cell Count Post-Week From 96 to End of Extension
The immunologic change was determined by Cluster of CD4+ cell count. CD4+ cell count post-Week 96 to end of extension were assessed.
Time frame: Week 96 to end of extension (up to 3 years)
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure and n (number analyzed) signifies participants analyzed for this outcome measure at specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | CD4+ Cell Count Post-Week From 96 to End of Extension | Week 96 + 6 months | 790.2 cells/mm^3 | Standard Error 17.23 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | CD4+ Cell Count Post-Week From 96 to End of Extension | Week 96 + 12 months | 779.4 cells/mm^3 | Standard Error 22.45 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | CD4+ Cell Count Post-Week From 96 to End of Extension | Week 96 + 18 months | 789.8 cells/mm^3 | Standard Error 23.43 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | CD4+ Cell Count Post-Week From 96 to End of Extension | Week 96 + 24 months | 781.9 cells/mm^3 | Standard Error 37.77 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | CD4+ Cell Count Post-Week From 96 to End of Extension | Week 96 + 30 months | 741.6 cells/mm^3 | Standard Error 37.12 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | CD4+ Cell Count Post-Week From 96 to End of Extension | Week 96 + 36 months | 784.7 cells/mm^3 | Standard Error 69.74 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | CD4+ Cell Count Post-Week From 96 to End of Extension | Week 96 + 30 months | 736.7 cells/mm^3 | Standard Error 37.47 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | CD4+ Cell Count Post-Week From 96 to End of Extension | Week 96 + 6 months | 749.7 cells/mm^3 | Standard Error 16.44 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | CD4+ Cell Count Post-Week From 96 to End of Extension | Week 96 + 24 months | 784.1 cells/mm^3 | Standard Error 30.78 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | CD4+ Cell Count Post-Week From 96 to End of Extension | Week 96 + 12 months | 774.3 cells/mm^3 | Standard Error 21.91 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | CD4+ Cell Count Post-Week From 96 to End of Extension | Week 96 + 36 months | 778.4 cells/mm^3 | Standard Error 86.59 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | CD4+ Cell Count Post-Week From 96 to End of Extension | Week 96 + 18 months | 758.4 cells/mm^3 | Standard Error 23.25 |
Secondary
Change From Baseline in Alkaline Phosphatase (ALP) Levels at Weeks 24 and 48
Change from baseline in ALP at Weeks 24 and 48 was reported.
Time frame: Baseline, Weeks 24 and 48
Population: BIS analysis set included all participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, 'n' (number analyzed) signifies participants analyzed for this outcome measure at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Alkaline Phosphatase (ALP) Levels at Weeks 24 and 48 | Week 24 | -3.2 Units per liter (U/L) | Standard Error 1.17 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Alkaline Phosphatase (ALP) Levels at Weeks 24 and 48 | Week 48 | -1.1 Units per liter (U/L) | Standard Error 1.29 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Alkaline Phosphatase (ALP) Levels at Weeks 24 and 48 | Week 24 | 12.0 Units per liter (U/L) | Standard Error 1.74 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Alkaline Phosphatase (ALP) Levels at Weeks 24 and 48 | Week 48 | 15.1 Units per liter (U/L) | Standard Error 2 |
Secondary
Change From Baseline in BMD T-score of Hip and Spine
BMD status was assessed using BMD T-scores; normal bone status was defined by a BMD T-score \>= -1, osteopenia by a T-score \>= -2.5 to \<-1.0, and osteoporosis by a T-score \<-2.5.
Time frame: Baseline, Weeks 24 and 48
Population: BIS analysis set included all participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, 'n' (number analyzed) signifies participants analyzed for this outcome measure at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in BMD T-score of Hip and Spine | Hip region BMD T-score (Week 24) | 0.019 BMD T-score | Standard Error 0.018 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in BMD T-score of Hip and Spine | Spine region BMD T-score (Week 24) | -0.121 BMD T-score | Standard Error 0.0259 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in BMD T-score of Hip and Spine | Hip region BMD T-score (Week 48) | 0.015 BMD T-score | Standard Error 0.0213 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in BMD T-score of Hip and Spine | Spine region BMD T-score (Week 48) | -0.061 BMD T-score | Standard Error 0.039 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in BMD T-score of Hip and Spine | Spine region BMD T-score (Week 48) | -0.225 BMD T-score | Standard Error 0.0386 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in BMD T-score of Hip and Spine | Hip region BMD T-score (Week 24) | -0.109 BMD T-score | Standard Error 0.0157 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in BMD T-score of Hip and Spine | Hip region BMD T-score (Week 48) | -0.177 BMD T-score | Standard Error 0.0225 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in BMD T-score of Hip and Spine | Spine region BMD T-score (Week 24) | -0.322 BMD T-score | Standard Error 0.0307 |
Secondary
Change From Baseline in Cluster of Differentiation-4 (CD4+) Cell Count at Week 48
The immunologic change was determined by changes in Cluster of CD4+ cell count. Change from baseline in CD4+ cell count at Week 48 were assessed.
Time frame: Baseline and Week 48
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Based on NC = F analysis with values after discontinuation imputed with the baseline value. Other (intermittent) missing values are imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Cluster of Differentiation-4 (CD4+) Cell Count at Week 48 | 190.49 Cells per millimeter cube (cells/mm^3) | Standard Error 10.472 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Cluster of Differentiation-4 (CD4+) Cell Count at Week 48 | 172.01 Cells per millimeter cube (cells/mm^3) | Standard Error 10.458 |
p-value: =0.21395% CI: [-10.595, 47.55]ANCOVA
Secondary
Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine by (Cockcroft-Gault Formula) at Week 48
Change from baseline in eGFRcr by cockcroft-gault formula at Week 48. The eGFRcr was assessed by calculated creatinine clearance (CrCl) using the Cockcroft-Gault formula, and was assessed using CrCl \[mL/min\] = (140 - A) \* W / (72 \* C) \* R. Where A is age at sample date \[years\], W is body weight at specific visit (kilogram \[kg\]), C is the serum concentration of creatinine \[mg/dL\], R = 1 if the participant is male and = 0.85 if female.
Time frame: Baseline and Week 48
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine by (Cockcroft-Gault Formula) at Week 48 | -5.16 milliliter per minute (mL/min) | Standard Error 0.79 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine by (Cockcroft-Gault Formula) at Week 48 | -11.20 milliliter per minute (mL/min) | Standard Error 0.802 |
p-value: <0.00195% CI: [3.83, 8.25]ANCOVA
Secondary
Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Formula at Week 48
Change from baseline in eGFRcr was calculated using the CKD-EPI equation as per which Stage 1 (normal or high GFR \[\>=90 mL/min\]); Stage 2 (Mild CKD \[60 to 90 mL/min\]); Stage 3 (Moderate CKD \[30 to 59mL/min\]); Stage 4 (Severe CKD \[15 to 29 mL/min\]); Stage 5 (End Stage CKD \[\<15 mL/min\]). The eGFRcr was assessed by calculating serum creatinine (Scr) using the equation: eGFRcr milliliter per minute per 1.72 meter square (mL/min/1.73m\^2) = 144\*(Scr/0.7)\^-0.329\*0.993\^age (Scr =\< 0.7 mg/dL) and eGFRcr mL/min/1.73m\^2 = 144\*(Scr/0.7)\^-1.209\*0.993\^age (Scr \>0.7 mg/dL) for female participants and eGFRcr mL/min/1.73m\^2 = 141\*(Scr/0.9)\^-0.411\*0.993\^age (Scr =\<0.9 mg/dL) and eGFRcr mL/min/1.73m\^2 = 141\*(Scr/0.9)\^-1.209\*0.993\^age (Scr \>0.9 mg/dL) for male participants.
Time frame: Baseline and Week 48
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Formula at Week 48 | -6.04 mL/min/1.73 m^2 | Standard Error 0.551 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Formula at Week 48 | -9.16 mL/min/1.73 m^2 | Standard Error 0.559 |
p-value: <0.00195% CI: [1.57, 4.66]ANCOVA
Secondary
Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst) by CKD-EPI Formula at Week 48
Change from baseline in eGFRcyst was calculated using the CKD-EPI equation as per which Stage 1 (normal or high GFR) \>= 90 indicates normal kidney function; Stage 2 (Mild CKD): 60 to 89 mL/min indicates mildly reduced kidney function; Stage 3 (Moderate CKD): 30 to 59 mL/min indicates moderately reduced kidney function; Stage 4 (Severe CKD): 15 to 29 mL/min indicates severely reduced kidney function; Stage 5 (End Stage of CKD): \<15 mL/min indicate very severe or end stage kidney failure. The eGFRcyst was assessed by calculated serum cystatin C (Scyst) using the equation: eGFRcyst mL/min/1.73m\^2 = 133 \* (Scyst/0,8)\^-0.499 \* 0.996\^age \[\* 0.932 if female\] (Scyst =\<0.8 mg/L) and eGFRcr mL/min/1.73m\^2 = 133 \* (Scyst/0,8)\^-1.328 \* 0.996\^age \[\* 0.932 if male\] (Scyst \>0.8 mg/L).
Time frame: Baseline and Week 48
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst) by CKD-EPI Formula at Week 48 | 5.32 mL/min/1.73 m^2 | Standard Error 0.525 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst) by CKD-EPI Formula at Week 48 | 2.92 mL/min/1.73 m^2 | Standard Error 0.532 |
p-value: =0.00195% CI: [0.93, 3.87]ANCOVA
Secondary
Change From Baseline in Levels of 25-Hydroxyvitamin D (25-OH Vitamin D), at Week 24 and 48
Change from baseline in 25-OH Vitamin D levels at Week 24 and 48 were reported.
Time frame: Baseline, Weeks 24 and 48
Population: BIS analysis set included all participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, 'n' (number analyzed) signifies participants analyzed for this outcome measure at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Levels of 25-Hydroxyvitamin D (25-OH Vitamin D), at Week 24 and 48 | Week 24 | 12.7 nanomol per liter (nmol/L) | Standard Error 2.76 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Levels of 25-Hydroxyvitamin D (25-OH Vitamin D), at Week 24 and 48 | Week 48 | 16.9 nanomol per liter (nmol/L) | Standard Error 2.84 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Levels of 25-Hydroxyvitamin D (25-OH Vitamin D), at Week 24 and 48 | Week 24 | 22.1 nanomol per liter (nmol/L) | Standard Error 3.76 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Levels of 25-Hydroxyvitamin D (25-OH Vitamin D), at Week 24 and 48 | Week 48 | 28.3 nanomol per liter (nmol/L) | Standard Error 3.15 |
Secondary
Change From Baseline in Levels of Parathyroid Hormone (PTH) at Weeks 24 and 48
Change from baseline in PTH at Weeks 24 and 48 were reported.
Time frame: Baseline, Weeks 24 and 48
Population: BIS analysis set included participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, 'n' (number analyzed) signifies participants analyzed for this outcome measure at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Levels of Parathyroid Hormone (PTH) at Weeks 24 and 48 | Week 24 | 0.113 Picomol per liter (pmol/L) | Standard Error 0.2171 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Levels of Parathyroid Hormone (PTH) at Weeks 24 and 48 | Week 48 | -0.004 Picomol per liter (pmol/L) | Standard Error 0.2232 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Levels of Parathyroid Hormone (PTH) at Weeks 24 and 48 | Week 48 | 0.633 Picomol per liter (pmol/L) | Standard Error 0.2155 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Levels of Parathyroid Hormone (PTH) at Weeks 24 and 48 | Week 24 | 0.777 Picomol per liter (pmol/L) | Standard Error 0.2401 |
Secondary
Change From Baseline in Levels of Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) at Weeks 24 and 48
Change from baseline in serum CTX at Weeks 24 and 48 were reported.
Time frame: Baseline, Weeks 24 and 48
Population: BIS analysis set included all participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, 'n' (number analyzed) signifies participants analyzed for this outcome measure at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Levels of Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) at Weeks 24 and 48 | Week 24 | 0.047 mcg/L | Standard Error 0.0165 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Levels of Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) at Weeks 24 and 48 | Week 48 | 0.046 mcg/L | Standard Error 0.0174 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Levels of Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) at Weeks 24 and 48 | Week 24 | 0.283 mcg/L | Standard Error 0.0251 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Levels of Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) at Weeks 24 and 48 | Week 48 | 0.226 mcg/L | Standard Error 0.0234 |
Secondary
Change From Baseline in Levels of Serum Procollagen 1 N-Terminal Propeptide (P1NP) at Weeks 24 and 48
Change from baseline in serum P1NP at Weeks 24 and 48 were reported.
Time frame: Baseline, Weeks 24 and 48
Population: BIS analysis set included all participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, 'n' (number analyzed) signifies participants analyzed for this outcome measure at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Levels of Serum Procollagen 1 N-Terminal Propeptide (P1NP) at Weeks 24 and 48 | Week 24 | 1.892 microgram per liter (mcg/L) | Standard Error 1.3754 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Levels of Serum Procollagen 1 N-Terminal Propeptide (P1NP) at Weeks 24 and 48 | Week 48 | 0.065 microgram per liter (mcg/L) | Standard Error 1.6428 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Levels of Serum Procollagen 1 N-Terminal Propeptide (P1NP) at Weeks 24 and 48 | Week 24 | 24.679 microgram per liter (mcg/L) | Standard Error 2.0956 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Levels of Serum Procollagen 1 N-Terminal Propeptide (P1NP) at Weeks 24 and 48 | Week 48 | 24.251 microgram per liter (mcg/L) | Standard Error 2.6337 |
Secondary
Change From Baseline in log10 HIV-1 RNA Levels at Week 48
Change from baseline in log10 HIV-1 RNA levels were reported.
Time frame: Baseline and Week 48
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Based on not completed (NC) equal to (=) failure (F) analysis with values after discontinuation imputed with the baseline value. Other (intermittent) missing values are imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in log10 HIV-1 RNA Levels at Week 48 | -2.95 log10 HIV-1 RNA copies per mL | Standard Error 0.044 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in log10 HIV-1 RNA Levels at Week 48 | -2.91 log10 HIV-1 RNA copies per mL | Standard Error 0.044 |
p-value: =0.43795% CI: [-0.171, 0.074]ANCOVA
Secondary
Change From Baseline in Serum Creatinine at Week 48
Change from baseline in serum creatinine at Week 48 was reported.
Time frame: Baseline and Week 48
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Serum Creatinine at Week 48 | 0.05 milligram per deciliter (mg/dL) | Standard Error 0.006 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Serum Creatinine at Week 48 | 0.09 milligram per deciliter (mg/dL) | Standard Error 0.006 |
p-value: <0.00195% CI: [-0.05, -0.02]ANCOVA
Secondary
Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) at Week 48
Change from baseline in UACR at Week 48 was reported.
Time frame: Baseline and Week 48
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) at Week 48 | -0.58 mg/g | Full Range -226.5 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) at Week 48 | -0.15 mg/g | Full Range -640.4 |
p-value: =0.033Wilcoxon rank sum test
Secondary
Change From Baseline in Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Week 48
Change from baseline in UB2MGCR at Week 48 were reported.
Time frame: Baseline and Week 48
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participant analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Week 48 | -30.42 mcg/g | Full Range -11818.6 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Week 48 | 18.36 mcg/g | Full Range -2440.5 |
p-value: <0.001Wilcoxon rank sum test
Secondary
Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Week 48
Change from baseline in UPCR at Week 48 was reported.
Time frame: Baseline and Week 48
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Week 48 | -15.72 milligram per gram (mg/g) | Full Range -748.1 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Week 48 | -10.53 milligram per gram (mg/g) | Full Range -903 |
p-value: =0.033Wilcoxon rank sum test
Secondary
Change From Baseline in Urine Retinol Binding Protein To Creatinine Ratio (URBPCR) at Week 48
Change from baseline in URBPCR at Week 48 were reported.
Time frame: Baseline and Week 48
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participant analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Baseline in Urine Retinol Binding Protein To Creatinine Ratio (URBPCR) at Week 48 | 7.00 microgram per gram (mcg/g) | Full Range -1555.7 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Baseline in Urine Retinol Binding Protein To Creatinine Ratio (URBPCR) at Week 48 | 35.02 microgram per gram (mcg/g) | Full Range -700.7 |
p-value: <0.001Wilcoxon rank sum test
Secondary
Change From Reference in ALP Levels
Change from reference in ALP levels at Week 96 was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The analysis population is BIS. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure. This outcome measure was planned to be reported for participants who received D/C/F/TAF in Test group and who switched to D/C/F/TAF in Switch to D/C/F/TAF group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in ALP Levels | -0.9 U/L | Standard Error 1.23 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in ALP Levels | -9.7 U/L | Standard Error 1.55 |
Secondary
Change From Reference in BMD T-score of Hip and Spine at Week 96
BMD status was assessed using BMD T-scores; normal bone status was defined by a BMD T-score \>= -1, osteopenia by a T-score \>= -2.5 to \<-1.0, and osteoporosis by a T-score \<-2.5. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The analysis set of BIS. Here, 'N' (number of participants analyzed) signifies participants evaluated for this outcome measure and n (number analyzed) signifies participants analyzed for this endpoint at specified category. This outcome measure was planned to be reported for participants who received D/C/F/TAF in Test group and who switched to D/C/F/TAF in Switch to D/C/F/TAF group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in BMD T-score of Hip and Spine at Week 96 | Hip region BMD T-score | -0.016 BMD T-score | Standard Error 0.0245 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in BMD T-score of Hip and Spine at Week 96 | Spine region BMD T-score | -0.090 BMD T-score | Standard Error 0.0407 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in BMD T-score of Hip and Spine at Week 96 | Hip region BMD T-score | 0.025 BMD T-score | Standard Error 0.0272 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in BMD T-score of Hip and Spine at Week 96 | Spine region BMD T-score | 0.034 BMD T-score | Standard Error 0.0355 |
Secondary
Change From Reference in CD4+ Cell Count at Week 96
The immunologic change was determined by changes in cluster of differentiation (CD4+) cell count. Change from reference in CD4+ cell count at Week 96 was assessed. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Based on NC=F analysis with values after discontinuation imputed with the baseline value. Other (intermittent) missing values are imputed using LOCF. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in CD4+ Cell Count at Week 96 | 228.85 cells/mm^3 | Standard Error 11.951 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in CD4+ Cell Count at Week 96 | 27.01 cells/mm^3 | Standard Error 9.522 |
Secondary
Change From Reference in eGFRcr by CKD-EPI Formula
Change from reference in eGFRcr was calculated using the CKD-EPI equation as per Stage 1 (normal or high GFR) to Stage 5 (End Stage of CKD). The eGFRcr was assessed by calculating serum creatinine (Scr) using the CKD-EPI equation: eGFRcr milliliter per minute per 1.72 meter square (mL/min/1.73m\^2) = 144 \* (Scr/0.7)\^-0.329 \* 0.993\^age (Scr =\< 0.7 mg/dL) and eGFRcr mL/min/1.73m\^2 = 144 \* (Scr/0.7)\^-1.209 \* 0.993\^age (Scr \>0.7 mg/dL) for female participants and eGFRcr mL/min/1.73m\^2 = 141 x (Scr/0.9)\^-0.411 x 0.993\^age (Scr =\<0.9 mg/dL) and eGFRcr mL/min/1.73m\^2 = 141 \* (Scr/0.9)\^-1.209 x 0.993\^age (Scr \>0.9 mg/dL) for male participants. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure. This outcome measure was planned to be reported for participants who received D/C/F/TAF in Test group and who switched to D/C/F/TAF in Switch to D/C/F/TAF group.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in eGFRcr by CKD-EPI Formula | -5.6 mL/min/1.73 m^2 | Full Range -33 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in eGFRcr by CKD-EPI Formula | 2.3 mL/min/1.73 m^2 | Full Range -29 |
Secondary
Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine by Cockcroft-Gault Formula
Change from reference in eGFRcr by cockcroft-gault formula was reported. The eGFRcr was assessed by calculated creatinine clearance (CrCl) using the Cockcroft-Gault formula, and was assessed using CrCl \[mL/min\] = (140 - A) \* W / (72 \* C) \* R. Where A is age at sample date \[years\], W is body weight at specific visit (kilogram \[kg\]), C is the serum concentration of creatinine \[mg/dL\], R = 1 if the participant is male and = 0.85 if female. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure. This outcome measure was planned to be reported for participants who received D/C/F/TAF in Test group and who switched to D/C/F/TAF in Switch to D/C/F/TAF group.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine by Cockcroft-Gault Formula | -5.2 mL/min | Full Range -73 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine by Cockcroft-Gault Formula | 4.6 mL/min | Full Range -47 |
Secondary
Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst) by CKD-EPI Formula
Change from reference in eGFRcyst was calculated using the CKD-EPI equation as per Stage 1 (normal or high GFR) to Stage 5 (End Stage of CKD): \<15 mL/min indicate very severe or end stage kidney failure. The eGFRcyst was assessed by calculated serum cystatin C (Scyst) using the CKD-EPI equation: eGFRcyst mL/min/1.73m\^2 = 133 \* (Scyst/0,8)\^-0.499 \* 0.996\^age \[x 0.932 if female\] (Scyst =\<0.8 mg/L) and eGFRcr mL/min/1.73m\^2 = 133 \* (Scyst/0,8)\^-1.328 \* 0.996\^age \[\* 0.932 if male\] (Scyst \>0.8 mg/L). Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure. This outcome measure was planned to be reported for participants who received D/C/F/TAF in Test group and who switched to D/C/F/TAF in Switch to D/C/F/TAF group.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst) by CKD-EPI Formula | 4.4 mL/min/1.73 m^2 | Full Range -14 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst) by CKD-EPI Formula | 0 mL/min/1.73 m^2 | Full Range -12 |
Secondary
Change From Reference in Levels of 25-OH Vitamin D
Change from reference in 25-OH Vitamin D were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: BIS analysis set included all participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure. This outcome measure was planned to be reported for participants who received D/C/F/TAF in Test group and who switched to D/C/F/TAF in Switch to D/C/F/TAF group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in Levels of 25-OH Vitamin D | 21.3 nmol/L | Standard Error 2.45 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in Levels of 25-OH Vitamin D | -10.3 nmol/L | Standard Error 2.87 |
Secondary
Change From Reference in Levels of PTH
Change from reference in PTH levels were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: BIS analysis set included all participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure. This outcome measure was planned to be reported for participants who received D/C/F/TAF in Test group and who switched to D/C/F/TAF in Switch to D/C/F/TAF group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in Levels of PTH | -0.290 pmol/L | Standard Error 0.2078 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in Levels of PTH | -1.283 pmol/L | Standard Error 0.2483 |
Secondary
Change From Reference in Levels of Serum CTX
Change from reference in serum CTX levels were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: BIS analysis set included all participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure. This outcome measure was planned to be reported for participants who received D/C/F/TAF in Test group and who switched to D/C/F/TAF in Switch to D/C/F/TAF group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in Levels of Serum CTX | 0.041 mcg/L | Standard Error 0.019 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in Levels of Serum CTX | -0.162 mcg/L | Standard Error 0.019 |
Secondary
Change From Reference in Levels of Serum P1NP
Change from reference in serum P1NP levels were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: BIS analysis set included all participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure. This outcome measure was planned to be reported for participants who received D/C/F/TAF in Test group and who switched to D/C/F/TAF in Switch to D/C/F/TAF group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in Levels of Serum P1NP | 2.817 mcg/L | Standard Error 1.714 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in Levels of Serum P1NP | -11.963 mcg/L | Standard Error 1.7636 |
Secondary
Change From Reference in log10 HIV-1 RNA Levels at Week 96
Change from reference in log10 HIV-1 RNA levels were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for Test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Based on not completed (NC) equal to (=) failure (F) analysis with values after discontinuation imputed with the baseline value. Other (intermittent) missing values are imputed using last observation carried forward (LOCF). Here N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in log10 HIV-1 RNA Levels at Week 96 | -2.72 log10 HIV-1 RNA copies per mL | Standard Error 0.0614 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in log10 HIV-1 RNA Levels at Week 96 | -0.0027 log10 HIV-1 RNA copies per mL | Standard Error 0.0131 |
Secondary
Change From Reference in Serum Creatinine
Change from reference in serum creatinine was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure. This outcome measure was planned to be reported for participants who received D/C/F/TAF in Test group and who switched to D/C/F/TAF in Switch to D/C/F/TAF group.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in Serum Creatinine | 0.045 mg/dL | Full Range -0.25 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in Serum Creatinine | -0.034 mg/dL | Full Range -0.71 |
Secondary
Change From Reference in UACR
Change from reference in UACR at Week 96 was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure. This outcome measure was planned to be reported for participants who received D/C/F/TAF in Test group and who switched to D/C/F/TAF in Switch to D/C/F/TAF group.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in UACR | -0.70 mg/g | Full Range -288.1 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in UACR | -0.49 mg/g | Full Range -294.5 |
Secondary
Change From Reference in UB2MGCR
Change from reference in UB2MGCR was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure. This outcome measure was planned to be reported for participants who received D/C/F/TAF in Test group and who switched to D/C/F/TAF in Switch to D/C/F/TAF group.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in UB2MGCR | -27.04 mcg/g | Full Range -11704.6 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in UB2MGCR | -40.53 mcg/g | Full Range -111778.9 |
Secondary
Change From Reference in UPCR
Change from reference in UPCR was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF+ FTC/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure. This outcome measure was planned to be reported for participants who received D/C/F/TAF in Test group and who switched to D/C/F/TAF in Switch to D/C/F/TAF group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in UPCR | -15.46 mg/g |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in UPCR | -1.40 mg/g |
Secondary
Change From Reference in URBPCR
Change from reference in URBPCR at Week 96 were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure. This outcome measure was planned to be reported for participants who received D/C/F/TAF in Test group and who switched to D/C/F/TAF in Switch to D/C/F/TAF group.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Change From Reference in URBPCR | 13.70 mcg/g | Full Range -1555.1 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Change From Reference in URBPCR | -35.53 mcg/g | Full Range -108886.3 |
Secondary
Number of Participants With ARV Resistance
Number of participants with DRV, FTC, TDF/TAF resistance were reported.
Time frame: Baseline to end of extension (up to 4 years)
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies total number of participants with screening/baseline and endpoint genotype.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Number of Participants With ARV Resistance | TFV RAMs | 0 Participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Number of Participants With ARV Resistance | DRV resistance-associated mutations (RAMs) | 0 Participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Number of Participants With ARV Resistance | FTC RAMs | 2 Participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Number of Participants With ARV Resistance | TFV RAMs | 0 Participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Number of Participants With ARV Resistance | DRV resistance-associated mutations (RAMs) | 0 Participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Number of Participants With ARV Resistance | FTC RAMs | 1 Participants |
| Switch to D/C/F/TAF | Number of Participants With ARV Resistance | DRV resistance-associated mutations (RAMs) | 0 Participants |
| Switch to D/C/F/TAF | Number of Participants With ARV Resistance | FTC RAMs | 2 Participants |
| Switch to D/C/F/TAF | Number of Participants With ARV Resistance | TFV RAMs | 0 Participants |
Secondary
Percentage of Participants With >95% Treatment Adherence Assessed by Drug Accountability
Treatment adherence assessed by drug accountability (based on pill count) from start of treatment/switch to last study drug intake by determination of the cumulative treatment adherence in participants who returned all dispensed bottles prior to or at the last visit in the study. Adherent participants were defined as having an adherence \>95% as assessed by drug accountability.
Time frame: Baseline to Switch and switch to EOE to Open-Label D/C/F/TAF (Up to 3 years)
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure and n (number analyzed) signifies participants analyzed for this outcome measure at specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With >95% Treatment Adherence Assessed by Drug Accountability | Baseline to Switch (double-blind treatment) | 87.2 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With >95% Treatment Adherence Assessed by Drug Accountability | Switch to End of Extension (open-label D/C/F/TAF) | 92.2 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With >95% Treatment Adherence Assessed by Drug Accountability | Baseline to Switch (double-blind treatment) | 82.6 percentage of participants |
| Switch to D/C/F/TAF | Percentage of Participants With >95% Treatment Adherence Assessed by Drug Accountability | Switch to End of Extension (open-label D/C/F/TAF) | 88.7 percentage of participants |
Secondary
Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 48
AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events. SAE is any adverse event (AE) that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: Up to Weeks 48
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 48 | Grade 3 AEs | 4.7 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 48 | Grade 4 AEs | 0.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 48 | SAEs | 4.7 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 48 | Premature discontinuations due to AEs | 1.9 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 48 | Premature discontinuations due to AEs | 4.4 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 48 | Grade 3 AEs | 4.4 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 48 | SAEs | 5.8 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 48 | Grade 4 AEs | 1.7 percentage of participants |
Secondary
Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 96
AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events. SAE is any adverse event (AE) that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: Up to Week 96
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. This outcome measure was planned to be reported for participants who received D/C/F/TAF in group 1 and who switched to D/C/F/TAF in group 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 96 | Grade 3 AEs | 11.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 96 | Grade 4 AEs | 0.8 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 96 | SAEs | 10.8 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 96 | Premature discontinuations due to AEs | 2.8 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 96 | Premature discontinuations due to AEs | 0.3 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 96 | Grade 3 AEs | 3.7 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 96 | SAEs | 2.7 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 96 | Grade 4 AEs | 1.4 percentage of participants |
Secondary
Percentage of Participants With Grade 3 and 4 AEs, SAEs, and Premature Discontinuations Due to Adverse Events Post-Week 96 to End of Extension
AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events. SAE is any adverse event (AE) that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: From Week 96 to end of extension (up to 3 years)
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Grade 3 and 4 AEs, SAEs, and Premature Discontinuations Due to Adverse Events Post-Week 96 to End of Extension | Grade 3 AEs | 3.5 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Grade 3 and 4 AEs, SAEs, and Premature Discontinuations Due to Adverse Events Post-Week 96 to End of Extension | Grade 4 AEs | 0 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Grade 3 and 4 AEs, SAEs, and Premature Discontinuations Due to Adverse Events Post-Week 96 to End of Extension | SAEs | 3.2 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Grade 3 and 4 AEs, SAEs, and Premature Discontinuations Due to Adverse Events Post-Week 96 to End of Extension | Premature discontinuations due to AEs | 1.0 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Grade 3 and 4 AEs, SAEs, and Premature Discontinuations Due to Adverse Events Post-Week 96 to End of Extension | Premature discontinuations due to AEs | 1.3 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Grade 3 and 4 AEs, SAEs, and Premature Discontinuations Due to Adverse Events Post-Week 96 to End of Extension | Grade 3 AEs | 5.2 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Grade 3 and 4 AEs, SAEs, and Premature Discontinuations Due to Adverse Events Post-Week 96 to End of Extension | SAEs | 4.8 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Grade 3 and 4 AEs, SAEs, and Premature Discontinuations Due to Adverse Events Post-Week 96 to End of Extension | Grade 4 AEs | 1.3 percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
Percentage of participants with HIV-1 RNA less than (\<) 20, 50, and 200 copies per mL at Weeks 48 and 96 based on TLOVR algorithm were assessed. TLOVR requires sustained HIV-1 RNA \< 50 copies per mL; confirmed HIV-1 RNA \>= 50 copies per mL is considered as non-response (rebound); participant is considered non-responder after permanent discontinuation.
Time frame: At Week 48 and 96
Population: The analysis population is ITT. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure and n (number analyzed) signifies participants analyzed for this OM for specific categories at specified timepoints. Participants received treatment from baseline till Week 48/Switch in control arm and from switch till Week 96 in Switch to D/C/F/TAF arm. Therefore, Week 96 and Week 48 data was not collected for both arms at respective timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | At Week 48: < 20 Copies per mL | 82.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | At Week 48: <50 Copies per mL | 91.2 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | At Week 48: <200 Copies per mL | 93.1 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | At Week 96: <20 Copies per mL | 73.2 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | At Week 96: <50 Copies per mL | 85.1 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | At Week 96: <200 Copies per mL | 86.7 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | At Week 48: < 20 Copies per mL | 79.9 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | At Week 48: <50 Copies per mL | 88.7 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | At Week 48: <200 Copies per mL | 91.7 percentage of participants |
| Switch to D/C/F/TAF | Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | At Week 96: <50 Copies per mL | 93.8 percentage of participants |
| Switch to D/C/F/TAF | Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | At Week 96: <20 Copies per mL | 78.4 percentage of participants |
| Switch to D/C/F/TAF | Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm | At Week 96: <200 Copies per mL | 96.9 percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA <20 and 200 Copies Per mL at Weeks 48 and 96 Defined by FDA Snapshot Approach
Percentage of participants with HIV-1 RNA \< 20/200 copies per mL using FDA snapshot approach were reported. The snapshot approach classified participants into 3 outcome categories: 1) virologic success (HIV RNA \< 20/50/200 copies per mL at Week 48 and 96), 2) virologic failure (HIV RNA \>= 20/50/200 copies per mL at Week 48 and 96), 3) no viral load data in the Week 48 and 96 visit window (discontinued due to adverse event/death/other reason). The missing HIV-1 RNA is considered as non-response.
Time frame: At Weeks 48 and 96
Population: The analysis population is ITT. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure and n (number analyzed) signifies participants analyzed for this OM for specific categories at specified timepoints. Participants received treatment from baseline till Week 48/Switch in control arm and from switch till Week 96 in Switch to D/C/F/TAF arm. Therefore, Week 96 and Week 48 data was not collected for both arms at respective timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV-1 RNA <20 and 200 Copies Per mL at Weeks 48 and 96 Defined by FDA Snapshot Approach | At week 48: <20 Copies per mL | 82.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV-1 RNA <20 and 200 Copies Per mL at Weeks 48 and 96 Defined by FDA Snapshot Approach | At week 48: <200 Copies per mL | 92.8 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV-1 RNA <20 and 200 Copies Per mL at Weeks 48 and 96 Defined by FDA Snapshot Approach | At week 96: <20 Copies per mL | 76.2 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV-1 RNA <20 and 200 Copies Per mL at Weeks 48 and 96 Defined by FDA Snapshot Approach | At week 96: <200 Copies per mL | 86.2 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV-1 RNA <20 and 200 Copies Per mL at Weeks 48 and 96 Defined by FDA Snapshot Approach | At week 48: <20 Copies per mL | 79.3 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV-1 RNA <20 and 200 Copies Per mL at Weeks 48 and 96 Defined by FDA Snapshot Approach | At week 48: <200 Copies per mL | 90.6 percentage of participants |
| Switch to D/C/F/TAF | Percentage of Participants With HIV-1 RNA <20 and 200 Copies Per mL at Weeks 48 and 96 Defined by FDA Snapshot Approach | At week 96: <200 Copies per mL | 96.9 percentage of participants |
| Switch to D/C/F/TAF | Percentage of Participants With HIV-1 RNA <20 and 200 Copies Per mL at Weeks 48 and 96 Defined by FDA Snapshot Approach | At week 96: <20 Copies per mL | 83.5 percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA <50 Copies Per mL at Week 96 Defined by FDA Snapshot Approach
Percentage of participants with a HIV-1 RNA \< 50 copies per mL were assessed using FDA snapshot approach which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. The snapshot approach classified participants into 3 outcome categories: 1) virologic success (HIV RNA \< 20/50/200 copies per mL at Week 96), 2) virologic failure (HIV RNA greater than or equal to \[\>=\] 20/50/200 copies per mL at Week 96), 3) no viral load data in the Week 96 visit window (discontinued due to adverse event/death/other reason). The missing HIV-1 RNA is considered as non-response.
Time frame: At Week 96
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV-1 RNA <50 Copies Per mL at Week 96 Defined by FDA Snapshot Approach | 85.1 percentage of participants | 95% Confidence Interval 81 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV-1 RNA <50 Copies Per mL at Week 96 Defined by FDA Snapshot Approach | 94.2 percentage of participants | 95% Confidence Interval 90.8 |
Secondary
Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension
Percentage of participants with HIV RNA \<50, \<20, and \<200 copies/mL post Week 96 to end of extension were reported.
Time frame: Week 96 to end of extension (up to 3 years)
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, 'N' (number of participants analyzed) signifies participants evaluated for this outcome measure and n (number analyzed) signifies participants analyzed for this outcome measure at specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 30 months (<50 copies/mL) | 94.7 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 24 months (<20 copies/mL) | 90.1 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 18 months (<50 copies/mL) | 98.1 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 30 months (<20 copies/mL) | 89.5 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 36 months (<50 copies/mL) | 100.0 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 36 months (<20 copies/mL) | 94.7 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 12 months (<50 copies/mL) | 99.0 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 6 months (<200 copies/mL) | 99.7 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 6 months (<20 copies/mL) | 85.8 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 24 months (<50 copies/mL) | 97.5 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 18 months (<200 copies/mL) | 98.7 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 12 months (<20 copies/mL) | 89.7 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 24 months (<200 copies/mL) | 97.5 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 6 months (<50 copies/mL) | 97.7 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 30 months (<200 copies/mL) | 96.5 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 18 months (<20 copies/mL) | 92.4 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 36 months (<200 copies/mL) | 100.0 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 12 months (<200 copies/mL) | 100.0 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 36 months (<200 copies/mL) | 87.5 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 6 months (<50 copies/mL) | 96.3 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 12 months (<50 copies/mL) | 96.7 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 18 months (<50 copies/mL) | 98.2 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 24 months (<50 copies/mL) | 95.7 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 30 months (<50 copies/mL) | 91.4 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 36 months (<50 copies/mL) | 68.8 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 6 months (<20 copies/mL) | 88.2 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 12 months (<20 copies/mL) | 91.6 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 18 months (<20 copies/mL) | 92.8 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 24 months (<20 copies/mL) | 87.0 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 30 months (<20 copies/mL) | 84.5 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 36 months (<20 copies/mL) | 62.5 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 6 months (<200 copies/mL) | 99.3 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 12 months (<200 copies/mL) | 99.5 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 18 months (<200 copies/mL) | 98.2 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 24 months (<200 copies/mL) | 97.8 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension | Week 96 + 30 months (<200 copies/mL) | 98.3 percentage of participants |
Secondary
Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates
Percentage of participants with non-PDVF by Kaplan-Meier Estimates were reported. PDVF was defined as having virologic non-response (HIV-1 RNA \<1 log10 reduction from baseline and \>=50 copies/mL at the Week 8 visit, confirmed at the next visit), virologic rebound (confirmed HIV-1 RNA \>=50 copies/mL after confirmed consecutive HIV-1 RNA \<50 copies/mL or confirmed \>1 log10 increase in HIV-1 RNA from nadir), or viremic at final time point (final available on treatment HIV-1 RNA \>=400 copies/mL).
Time frame: From Week 96 to end of extension (up to 2 years and 6 months)
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates | Week 96 | 100 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates | Week 96 + 6 months | 99.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates | Week 96 + 12 months | 99.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates | Week 96 + 18 months | 98.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates | Week 96 + 24 months | 97.3 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates | Week 96 + 30 months | 97.3 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates | Week 96 + 24 months | 97.8 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates | Week 96 | 100 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates | Week 96 + 18 months | 97.8 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates | Week 96 + 6 months | 99.2 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates | Week 96 + 30 months | 92.5 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates | Week 96 + 12 months | 99.2 percentage of participants |
Secondary
Percentage of Participants With PDVF Post-week 96 to End of Extension
Percentage of participants with PDVF were reported. Protocol-defined virologic failure was defined as having virologic non-response (HIV-1 RNA \<1 log10 reduction from baseline and \>=50 copies/mL at the Week 8 visit, confirmed at the next visit), virologic rebound (confirmed HIV-1 RNA \>=50 copies/mL after confirmed consecutive HIV-1 RNA \<50 copies/mL or confirmed \>1 log10 increase in HIV-1 RNA from nadir), or viremic at final time point (final available on treatment HIV-1 RNA \>=400 copies/mL).
Time frame: Week 96 to end of extension (up to 3 years)
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here N (number of participants analyzed) refers to 311 for test group and 310 for switch to D/C/F/TAFgroup in below table.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With PDVF Post-week 96 to End of Extension | Participants who met PDVF | 1.0 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With PDVF Post-week 96 to End of Extension | Virologic non-response | 0 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With PDVF Post-week 96 to End of Extension | Virologic rebound | 1.0 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With PDVF Post-week 96 to End of Extension | Viremic at final time point | 0 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With PDVF Post-week 96 to End of Extension | Viremic at final time point | 0.7 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With PDVF Post-week 96 to End of Extension | Participants who met PDVF | 2.1 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With PDVF Post-week 96 to End of Extension | Virologic rebound | 1.4 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With PDVF Post-week 96 to End of Extension | Virologic non-response | 0 percentage of participants |
Secondary
Percentage of Participants With Protocol-defined Virologic Failure (PDVF)
Percentage of participants with PDVF were reported. Protocol-defined virologic failure was defined as having virologic non-response (HIV-1 RNA \<1 log10 reduction from baseline and \>=50 copies/mL at the Week 8 visit, confirmed at the next visit), virologic rebound (confirmed HIV-1 RNA \>=50 copies/mL after confirmed consecutive HIV-1 RNA \<50 copies/mL or confirmed \>1 log10 increase in HIV-1 RNA from nadir), or viremic at final time point (final available on treatment HIV-1 RNA \>=400 copies/mL).
Time frame: From Baseline up to Week 96
Population: The analysis population is ITT. Here, n (number analyzed) signifies participants analyzed for this OM at specified timepoints. Participants received treatment from baseline till Week 48/Switch in control arm and from switch till Week 96 in Switch to D/C/F/TAF arm. Therefore, Week 96 and Week 48 data was not collected for both arms at respective timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Protocol-defined Virologic Failure (PDVF) | Participants who met PDVF (Baseline - Week 96) | 4.1 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Protocol-defined Virologic Failure (PDVF) | Virologic non-response (Baseline - Week 96) | 0.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Protocol-defined Virologic Failure (PDVF) | Virologic rebound (Baseline-Week 96) | 0.3 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Protocol-defined Virologic Failure (PDVF) | Viremic at final time point (Baseline-Week 96) | 0.6 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Protocol-defined Virologic Failure (PDVF) | Participants who met PDVF (Baseline - Switch) | 4.4 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Protocol-defined Virologic Failure (PDVF) | Virologic non-response (Baseline - Switch) | 0 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Protocol-defined Virologic Failure (PDVF) | Virologic rebound (Baseline - Switch) | 3.9 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Protocol-defined Virologic Failure (PDVF) | Viremic at final time point (Baseline - Switch) | 0.6 percentage of participants |
| Switch to D/C/F/TAF | Percentage of Participants With Protocol-defined Virologic Failure (PDVF) | Participants who met PDVF (Switch - Week 96) | 1.1 percentage of participants |
| Switch to D/C/F/TAF | Percentage of Participants With Protocol-defined Virologic Failure (PDVF) | Virologic non-response (Switch - Week 96) | 0 percentage of participants |
| Switch to D/C/F/TAF | Percentage of Participants With Protocol-defined Virologic Failure (PDVF) | Virologic rebound (Switch - Week 96) | 1.1 percentage of participants |
| Switch to D/C/F/TAF | Percentage of Participants With Protocol-defined Virologic Failure (PDVF) | Viremic at final time point (Switch - Week 96) | 0 percentage of participants |
Secondary
Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates
Percentage of participants with time to treatment failure by Kaplan-Meier Estimates were reported. Treatment failure was defined as having either protocol-defined virologic failure or having discontinued for reasons other than alternate access to D/C/F/TAF (or other ARVs).
Time frame: From Week 96 to end of extension (up to 3 years)
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, n (number analyzed) signifies participants analyzed for this OM at specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates | Week 96 + 36 months | 84.8 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates | Week 96 + 6 months | 98.9 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates | Week 96 + 12 months | 95.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates | Week 96 + 18 months | 90.6 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates | Week 96 + 24 months | 87.1 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates | Week 96 + 30 months | 84.8 percentage of participants |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates | Week 96 | 100 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates | Week 96 | 100 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates | Week 96 + 18 months | 89.5 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates | Week 96 + 6 months | 97.4 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates | Week 96 + 30 months | 79.1 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates | Week 96 + 12 months | 94.1 percentage of participants |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates | Week 96 + 24 months | 86.4 percentage of participants |
Secondary
Percent Change From Baseline in Hip and Spine Bone Mineral Density (BMD)
The BMD is the amount of mineral in gram per square centimeter of bone, which was assessed by dual energy x-ray absorptiometry (DEXA) scan. Positive values are best values and negative values are worst values of change. Percent change from baseline in hip and spine BMD was assessed.
Time frame: Baseline, Weeks 24 and 48
Population: Bone investigation substudy (BIS) analysis set included all participants who were randomized, received at least 1 dose of study drug in study and had at least one post-baseline value for either biomarker/BMD data. Here, n (number analyzed) signifies participants analyzed for this OM at specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percent Change From Baseline in Hip and Spine Bone Mineral Density (BMD) | Hip region BMD (Week 24) | 0.29 Percent change | Standard Error 0.248 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percent Change From Baseline in Hip and Spine Bone Mineral Density (BMD) | Hip region BMD (Week 48) | 0.17 Percent change | Standard Error 0.322 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percent Change From Baseline in Hip and Spine Bone Mineral Density (BMD) | Spine region BMD (Week 48) | -0.68 Percent change | Standard Error 0.402 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percent Change From Baseline in Hip and Spine Bone Mineral Density (BMD) | Spine region BMD (Week 24) | -1.34 Percent change | Standard Error 0.285 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percent Change From Baseline in Hip and Spine Bone Mineral Density (BMD) | Spine region BMD (Week 48) | -2.38 Percent change | Standard Error 0.428 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percent Change From Baseline in Hip and Spine Bone Mineral Density (BMD) | Hip region BMD (Week 24) | -1.66 Percent change | Standard Error 0.269 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percent Change From Baseline in Hip and Spine Bone Mineral Density (BMD) | Spine region BMD (Week 24) | -3.43 Percent change | Standard Error 0.309 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percent Change From Baseline in Hip and Spine Bone Mineral Density (BMD) | Hip region BMD (Week 48) | -2.69 Percent change | Standard Error 0.342 |
Comparison: Hip region BMD (Week 24)p-value: <0.00195% CI: [1.227, 2.678]ANCOVA
Comparison: Hip region BMD (Week 48)p-value: <0.00195% CI: [1.934, 3.791]ANCOVA
Comparison: Spine region BMD (Week 24)p-value: <0.00195% CI: [1.259, 2.919]ANCOVA
Comparison: Spine region BMD (Week 48)p-value: =0.00495% CI: [0.539, 2.858]ANCOVA
Secondary
Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Week 48
Percent change from baseline in FEPO4 at Week 48 was reported.
Time frame: Baseline and Week 48
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, N (number of participants analyzed) signifies participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Week 48 | 16.00 Percent change | Full Range -87.3 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Week 48 | 22.55 Percent change | Full Range -90.1 |
p-value: =0.147Wilcoxon rank sum test
Secondary
Percent Change From Reference in Hip and Spine BMD
The BMD is the amount of mineral in gram per square centimeter of bone, which was assessed by DEXA scan. Positive values are best values and negative values are worst values of change. Percent change from reference in hip and spine BMD was assessed. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The analysis population is BIS. Here, 'N' (number of participants analyzed) signifies participants evaluated for this outcome measure and 'n' (number analyzed) signifies participants analyzed for this outcome measure at specified category. This outcome measure was planned to be reported for participants who received D/C/F/TAF in Test group and who switched to D/C/F/TAF in Switch to D/C/F/TAF group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percent Change From Reference in Hip and Spine BMD | Hip region BMD | -0.2565 Percent change in BMD | Standard Error 0.35599 |
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percent Change From Reference in Hip and Spine BMD | Spine region BMD | -0.9349 Percent change in BMD | Standard Error 0.44599 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percent Change From Reference in Hip and Spine BMD | Hip region BMD | 0.5467 Percent change in BMD | Standard Error 0.38512 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percent Change From Reference in Hip and Spine BMD | Spine region BMD | 0.4829 Percent change in BMD | Standard Error 0.3927 |
Secondary
Percent Change From Reference in Urine FEPO4
Percent change from reference in FEPO4 at Week 96 were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.
Time frame: From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Population: The ITT analysis set included all the participants who were randomized and received at least one dose of study treatment in the study. Here, 'N' (number of participants analyzed) signifies participants evaluated for this outcome measure. This outcome measure was planned to be reported for participants who received D/C/F/TAF in Test group and who switched to D/C/F/TAF in Switch to D/C/F/TAF group.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Percent Change From Reference in Urine FEPO4 | 18.52 Percent change in urine FEPO4 | Full Range -84.2 |
| DRV/COBI+ FTC/TDF (Control) (Baseline to Switch) | Percent Change From Reference in Urine FEPO4 | -7.51 Percent change in urine FEPO4 | Full Range -83.5 |
Secondary
Plasma Concentrations 2 Hours After Dosing (C0-2h) of Tenofovir Alafenamide
C0-2h is defined as the plasma concentrations 2 hours after dosing.
Time frame: 0 to 2 hours post dose
Population: PK analysis set included all participants who were randomized, received at least 1 dose of study drug and plasma concentration data for analytes of interest were available. PK data of TAF was analyzed only for test arm as per planned analyses. Here, 'N' (number of participants analyzed) number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Plasma Concentrations 2 Hours After Dosing (C0-2h) of Tenofovir Alafenamide | 11.9785 ng/mL | Standard Deviation 11.86104 |
Secondary
Predose (Trough) Plasma Concentration (C0h) of Darunavir
C0h is defined as the predose (trough) plasma concentration or concentration just prior to study drug administration.
Time frame: 30 minutes to 4 hours postdose at Weeks 2, 4, 12, 24 and 48 and at 2 timepoints with at least 2.5 hours in between sampling at Week 8 and 36 (first sample between 1 and 4 hours postdose)
Population: PK analysis set included all participants who were randomized, received at least 1 dose of study drug and plasma concentration data for analytes of interest were available. PK data of DRV was analyzed only for test arm as per planned analyses. Here, 'N' (number of participants analyzed) number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D/C/F/TAF (Test) (Baseline to End of Extension [EOE]) | Predose (Trough) Plasma Concentration (C0h) of Darunavir | 1898.9100 nanogram per milliliter (ng/mL) | Standard Deviation 758.83837 |